title: Arl13b-regulated cilia activities are essential for polarized radial glial scaffold formation.
abstract: The construction of cerebral cortex begins with the formation of radial glia. Once formed, polarized radial glial cells divide either symmetrically or asymmetrically to balance appropriate production of progenitor cells and neurons. Following birth, neurons use the processes of radial glia as scaffolding for oriented migration. Radial glia therefore provide an instructive structural matrix to coordinate the generation and placement of distinct groups of cortical neurons in the developing cerebral cortex. We found that Arl13b, a cilia-enriched small GTPase that is mutated in Joubert syndrome, was critical for the initial formation of the polarized radial progenitor scaffold. Using developmental stage-specific deletion of Arl13b in mouse cortical progenitors, we found that early neuroepithelial deletion of ciliary Arl13b led to a reversal of the apical-basal polarity of radial progenitors and aberrant neuronal placement. Arl13b modulated ciliary signaling necessary for radial glial polarity. Our findings indicate that Arl13b signaling in primary cilia is crucial for the initial formation of a polarized radial glial scaffold and suggest that disruption of this process may contribute to aberrant neurodevelopment and brain abnormalities in Joubert syndrome-related ciliopathies.
authors.affiliation: University of North Carolina Neuroscience Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
authors.forename: Holden
authors.initials: H
authors.lastname: Higginbotham
authors.forename: Jiami
authors.initials: J
authors.lastname: Guo
authors.forename: Yukako
authors.initials: Y
authors.lastname: Yokota
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Umberger
authors.forename: Chen-Ying
authors.initials: CY
authors.lastname: Su
authors.forename: Jingjun
authors.initials: J
authors.lastname: Li
authors.forename: Nisha
authors.initials: N
authors.lastname: Verma
authors.forename: Joshua
authors.initials: J
authors.lastname: Hirt
authors.forename: Vladimir
authors.initials: V
authors.lastname: Ghukasyan
authors.forename: Tamara
authors.initials: T
authors.lastname: Caspary
authors.forename: E S
authors.initials: ES
authors.lastname: Anton
mesh_terms: D020727:ADP-Ribosylation Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D000015:Abnormalities, Multiple; D000818:Animals; D054468:Axoneme / Q000648:ultrastructure; D002455:Cell Division; D016764:Cell Polarity; D002526:Cerebellar Diseases / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002531:Cerebellum / Q000002:abnormalities; D002540:Cerebral Cortex / Q000002:abnormalities / Q000196:embryology / Q000254:growth & development; D002552:Cerebral Ventricles / Q000002:abnormalities; D002923:Cilia / Q000201:enzymology* / Q000502:physiology; D004848:Epithelium / Q000648:ultrastructure; D005124:Eye Abnormalities / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D058953:Neural Stem Cells / Q000502:physiology / Q000648:ultrastructure; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology*; D009457:Neuroglia / Q000502:physiology / Q000648:ultrastructure*; D012160:Retina / Q000002:abnormalities / Q000201:enzymology / Q000473:pathology; D013687:Telencephalon / Q000196:embryology / Q000648:ultrastructure
chemical_list: C560093:Arl13b protein, mouse; D009419:Nerve Tissue Proteins; D020727:ADP-Ribosylation Factors; C530391:ARL13B protein, human